Despite many decades of study, schizophrenia remains a poorly understood neurologicaldisorder.However, clinical and experimental studies have implicated dopaminergic, serotoriergic, and glutamatergicneurotransmission in the pathophysiology of this debilitatingpsychiatric disorder. A better understandingof the intracellular signal Iransduction mechanisms linked to these neurotransmitters may more effective treatments for this disease. The responsibilities of the Molecular and Biochemical Core will be to provide a foundation for many of the studies of neuroleptic drug action proposed in Projects 1-5. The Core will perform tasks ranging from sophisticatedscreens that will identify novel protein-protein interactions to basic molecular biology and routine biochemistry that will aid in the investigation these studies. The Core will also provide a technical support facility for the performanceof routine tasks that will be required to accomplish the studies described in Projects 1-5 in an efficient and cosl-effective manner. Thesi tasks will be to maintain stocks of purified protein kinases, protein phosphatases, affinity-purified antibodies, and substrate proteins. Standard purification protocols will be used to obtain these enzymes from native sources, and recombinant technologies will also be employed to produce specific proteins in quantities sufficient to carry out detailed enzymological and structural studies. The Core will also supervise the productionand testing of new polydonal anti-peptide antibodies and phosphorylation state-specific antibodies.